Senescent Cell‐Derived Extracellular Vesicles in Therapy‐Induced Senescence: Immune Remodelling and Emerging Links to Mitochondrial Stress in Cancer

Abstract

ABSTRACT Cancer therapy can induce cellular senescence and remodel the tumour microenvironment through the senescence‐associated secretory phenotype (SASP), including its membrane‐enclosed component, senescent cell‐derived extracellular vesicles (senEVs). This review summarizes senEV biogenesis, cargo‐dependent functions, and immune‐remodelling effects while distinguishing mechanisms directly demonstrated in experimentally validated senescent‐cell EV models from contextual evidence derived from broader EV and mitochondrial‐stress studies. Direct evidence shows that senEVs can support immune‐mediated clearance in some models or promote tumour growth, chemoresistance, and polymorphonuclear myeloid‐derived suppressor cell (PMN‐MDSC)‐mediated immunosuppression in others. We further evaluate mitochondrial stress and EV‐associated mitochondrial DNA as an emerging mechanistic framework that may contribute to these divergent outcomes, rather than as an established general regulator of senEV activity. Finally, we discuss candidate intervention strategies, evidence gaps, and the experimental requirements needed to define how donor‐cell state, cargo composition, recipient‐cell identity, treatment context and time after treatment may shape senEV function.